Department of Zoology, Bodoland University, Kokrajhar, Assam, India.
Microbiology Laboratory, Bioinformatics Division, Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi, Bangladesh.
J Biomol Struct Dyn. 2022 Mar;40(5):2067-2081. doi: 10.1080/07391102.2020.1835729. Epub 2020 Oct 22.
COVID-19 and its causative organism SARS-CoV2 that emerged from Wuhan city, China have paralyzed the world. With no clinically approved drugs, the global health system is struggling to find an effective treatment measure. At this crucial juncture, screening of plant-derived compounds may be an effective strategy to combat COVID-19. The present study investigated the binding affinity of phytocompounds with 3-Chymotrypsin-like (3CLpro) and Papain-like proteases (PLpro) of SARS-CoV2 using techniques. A total of 32 anti-protease phytocompounds were investigated for the binding affinity to the proteins. Docking was performed in Autodock Vina. Pharmacophore descriptors of best ligands were studied using LigandScout. Molecular dynamics (MD) simulation of apo-protein and ligand-bound complexes was carried out in YASARA software. The druglikeness properties of phytocompounds were studied using ADMETlab. Out of 32 phytochemicals, amentoflavone and gallocatechin gallate showed the best binding affinity to 3CLpro (-9.4 kcal/mol) and PLpro (-8.8 kcal/mol). Phytochemicals such as savinin, theaflavin-3,3-digallate, and kazinol-A also showed strong affinity. MD simulation revealed ligand-induced conformational changes in the protein with decreased surface area and higher stability. The RMSD/F of proteins and ligands showed stability of the protein suggesting the effective binding of the ligand in both the proteins. Both amentoflavone and gallocatechin gallate possess promising druglikeness property. The present study thus suggests that Amentoflavone and Gallocatechin gallate may be potential inhibitors of 3CLpro and PLpro proteins and effective drug candidates for SARS-CoV2. However, the findings of study need to be supported by studies to establish the exact mode of action.Communicated by Ramaswamy H. Sarma.
新型冠状病毒肺炎（COVID-19）及其源自中国武汉市的病原体 SARS-CoV2 已使全球陷入瘫痪。由于没有经过临床批准的药物，全球卫生系统正在努力寻找有效的治疗措施。在这一关键时刻，筛选植物来源的化合物可能是对抗 COVID-19 的有效策略。本研究使用 技术研究了植物化合物与 SARS-CoV2 的 3-糜蛋白酶样（3CLpro）和木瓜蛋白酶样蛋白酶（PLpro）的结合亲和力。共研究了 32 种抗蛋白酶植物化合物与蛋白质的结合亲和力。对接在 Autodock Vina 中进行。使用 LigandScout 研究了最佳配体的药效团描述符。在 YASARA 软件中进行了 apo-蛋白和配体结合复合物的分子动力学（MD）模拟。使用 ADMETlab 研究了植物化合物的药物性质。在 32 种植物化学物质中，芹菜素和没食子儿茶素没食子酸酯对 3CLpro（-9.4 kcal/mol）和 PLpro（-8.8 kcal/mol）表现出最佳的结合亲和力。芹菜素、茶黄素-3,3-二没食子酸酯和 Kazinol-A 等植物化学物质也表现出很强的亲和力。MD 模拟显示，配体诱导蛋白质构象发生变化，表面积减小，稳定性提高。蛋白质和配体的 RMSD/F 表明蛋白质稳定，提示配体在两种蛋白质中均有效结合。芹菜素和没食子儿茶素没食子酸酯均具有良好的药物性质。因此，本研究表明，芹菜素和没食子儿茶素没食子酸酯可能是 3CLpro 和 PLpro 蛋白的潜在抑制剂，也是 SARS-CoV2 的有效候选药物。然而，研究结果需要进一步的研究来支持，以确定其确切的作用模式。
